Pharmacology Lesson 1 (NCM 106) PDF

PHARMACOLOGY NCM 106 PROF. DANLLED JAVIER | S.Y 2024-2025 | DOMINGO,ANGELYN LESSON 1: DRUGS AFFECTING THE AUTONOMIC NERVOUS SYSTEM...

PHARMACOLOGY NCM 106 PROF. DANLLED JAVIER | S.Y 2024-2025 | DOMINGO,ANGELYN LESSON 1: DRUGS AFFECTING THE AUTONOMIC NERVOUS SYSTEM 1.2 PARASYMPATHETIC NERVOUS SYSTEM NERVOUS SYTEM “rest and digest” ADRENERGIC AGONISTS AND ANTAGONISTS Digestive processes promoted; HR and BP declined. originates from the craniosacral region (CN 3,7,9,10 and Sacral nerves 2 and 4) CHOLINERGIC AGONISTS AND ANTAGONISTS NOTE: These divisions often work antagonistically to regulate physiological functions. NERVOUS SYSTEM NOTE: Dilation of Eyes is called mynasis and Constriction of eyes called miosis SENSORY NEURONS sensory organs to CNS CENTRAL NERVOUS SYTEM (CNS) BRAIN receives and processes sensory information, initiates response, stores memories, generates thoughts and emotions. SPINAL CORD conducts signals to and from the brain, controls reflex activities. PERIPHERAL NERVOUS SYTEM (PNS) MOTOR NEURONS CNS to muscle and glands SOMATICS NERVOUS SYSTEM Controls voluntary movements activates skeletal muscles; VOLUNTARY AUTONOMIC NERVOUS SYSTEM Controls involuntary responses influences organs, glands, smooth muscles; INVOLUNTARY plays a pivotal role in regulating involuntary bodily functions, including heart rate, digestion, respiratory rate, and pupillary response. 1.1 SYMPATHETIC NERVOUS SYSTEM “fight or flight” It readies the body for an immediate response to a potential threat. e.g. stressful situation CNS PNS arises from the thoracolumbar region (T1-T12 and L2-L3) Brain and Spinal Cord Sensory Neurons PREGANGLIONIC REGION Motor Neurons is made up of “fibers” that exit through the thoracolumbar spinal nerves. somatic nervous system Cholinergic fibers = Acetylcholine (AChE) autonomic nervous system Memory, learning, attention, arousal and involuntary muscle movement ◦parasympathetic Postganglionic neurons contains “adrenergic fibers” (Norapinephrine, Epinephrine, and Dopamine) ◦sympathetic POSTGANGLIONIC REGION Adrenergic fibers = Norepinephrine (NE) Neurotransmitter which acts on alpha and beta receptors HR, bronchodilation, mydriasis, etc. FOUR MAIN RECEPTORS ALPHA 1 RECEPTORS located in the blood vessels, eyes, bladder, and prostate Alpha-1 receptors are found in the walls of blood vessels. When these receptors are activated, they cause the muscles around the blood vessels to tighten (vasoconstriction). This tightening makes the blood vessels narrower, which increases blood pressure. Alpha-1 receptors increases heart contractions, helping pump blood more effectively and raising blood pressure Eyes will dilate (mydriasis) Bladder will relaxed Prostate will contract NOTE: Norepinephrine and Epinephrine are release in adrenal gland  PHARMACOLOGY NCM 106 PROF. DANLLED JAVIER | S.Y 2024-2025 | DOMINGO,ANGELYN ALPHA 2 RECEPTORS NURSING CONSIDERATION located in the postganglionic sympathetic nerve endings that INHIBIT NE release– blood vessels and Known hypersensitivity to phenylephrine smooth muscles Severe hypertension, ventricular tachycardia Alpha-2 receptors, when activated, cause a reduction in the release of norepinephrine, a chemical that Caution in neonates with hyperthyroidism, hypertension, myocardial disease, heart block, typically narrows blood vessels. With less norepinephrine, the blood vessels relax (widen), leading to a bradycardia, bronchopulmonary dysplasia, and narrow-angle glaucoma decrease in blood pressure. Blood pressure and heart rate should be monitored. When activated, they reduce the tone and movement (motility) of the GI tract, slowing down the process of digestion and movement of food. Epinephrine, Ephedrine, Dopamine, Phenylephrine, Midodrine An α1-adrenergic receptor agonist exerts its actions via activation of α1 -adrenergic receptors of the arteriolar and venous vasculature, producing an increase in vascular tone and elevation of blood pressure. BETA 1 RECEPTORS located primarily in the heart but also in the kidneys. Stimulation increases myocardial contraction and NURSING CONSIDERATION heart rate. May cause hypertension, paresthesias, pruritus, abdominal pain, urinary retention/urgency, dysuria Blood pressure checks and a kidney function blood test should be carried out before starting Heart Kidney midodrine. Blood pressure and heart rate should be monitored during treatment with midodrine. It is especially Increase heart contraction Increase renin secretion important to have your blood pressure checked after lying down. Increase heart rate Increase angiotensin ALPHA 2 AGONIST Increase blood pressure Clonidine, Methyldopa BETA 2 RECEPTORS Smooth muscle (GI Lungs Uterus Liver Tract) Decrease GI tone and Relaxation of uterine Activiation of Bronchodilation motility smooth muscle glycogenolysis Increased blood sugar Stimulates alpha-2 adrenoreceptors in the brain stem. This results in reduced sympathetic outflow from ADRENERGIC AGONISTS DRUGS the central nervous system and decreases in peripheral resistance, renal vascular resistance, heart rate and blood pressure Adrenergic agonists, adrenergic, sympathomimetics They mimic the sympathetic neurotransmitters NE and Epi. NURSING CONSIDERATION CLASSIFICATION OF SYMPATHOMIMETICS Monitor blood pressure and pulse rate frequently. Dosage is usually adjusted to the patient’s blood pressure and can cause hypotension, bradycardia, and sedation. DIRECT-ACTING SYMPATHOMIMETICS Rebound hypertension may occur if stopped abruptly. May cause dizziness, drowsiness, confusion, fatigue, pruritus, nausea, vomiting, abdominal pain, Directly stimulate the adrenergic receptors constipation, dry mouth, orthostatic hypotension, bradycardia, anxiety, edema E.g. Epinephrine, Norepinephrine Clonidine, Methyldopa NOTE: Epinephrine is for anaphylactic shock and allergic reaction INDIRECT-ACTING SYMPATHOMIMETICS Stimulates the release of NE from the terminal nerve endings E.g. Amphetamine (ADHD, narcolepsy) MIXED-ACTING SYMPATHOMIMETICS Stimulates the adrenergic receptor sites and release of NE from the terminal nerve endings E.g. Ephedrine (perioperative hypotension) Works by binding to alpha(α)-2 adrenergic receptors as an agonist, inhibiting adrenergic neuronal ALPHA 1 AGONISTS outflow and reducing vasoconstrictor adrenergic signals. Catapres: can cause rebound hypertension so dapat gradual lang yung paghinto sa pag-take Epinephrine, Ephedrine, Dopamine, Phenylephrine, Midodrine : e.g. from 0.5 ml to.0.4 ml to 0.4 ml...... stop Aldomet: use to treat pre- eclampsia and gestational hypertension NOTE: in 20th weeks of pregnancy blood pressure increases that can lead to pre- eclampsia NOTE: Aldomet can sometimes cause hemolytic anemia by triggering the production of antibodies against red blood cells. The Coombs test is used to confirm this by detecting the presence of these antibodies on the surface of red blood cells. BETA 1 AGONIST Epinephrine, Ephedrine, Dopamine, Dobutamine, Isoproterenol Activation of α1-adrenoceptors in the arterioles of the nasal mucosa with little effect on the beta receptors of the heart, lacking chronotropic and inotropic actions on the heart. NOTE: Phenylephrine is not allowed to patient with high blood pressure NOTE:NARROW ANGLE GLUCOMA can increase intraocular pressure NOTE: Intraocular Pressure- dilated eye, phenylephrine can cause increased pressure in the eye that can cause blindness or pagkalabo ng mata.  PHARMACOLOGY NCM 106 PROF. DANLLED JAVIER | S.Y 2024-2025 | DOMINGO,ANGELYN Inhibits alpha1-adrenergic receptors by promoting peripheral arterial and venous dilation and reduces NURSING CONSIDERATION peripheral vascular resistance, thereby lowering blood pressure. Relaxes smooth muscle of the bladder neck, prostate, and prostate capsule, which reduces urethral Avoid giving dobutamine to patients with uncorrected hypovolemia. Expect prescriber to order resistance and pressure and urinary outflow resistance. whole blood or plasma volume expanders to correct hypovolemia Also avoid giving dobutamine to patients with acute MI because it can intensify or extend myocardial ischemia. NURSING CONSIDERATION Use drug cautiously in patients allergic to sulfites because drug may cause anaphylactic-like signs Be aware that prostate cancer should be ruled out before giving treatment for BPH begins. and symptoms. Expect prescriber to reduce dosage if a diuretic or another antihypertensive is added to patient’s Dilute concentrate with at least 50 ml compatible I.V. solution. A common dilution is 500 mg (40 ml regimen. from 250-ml bag) in 210 ml D5W or NSS to yield 2,000 mcg/ml. Or dilute 1,000 mg (80 ml from 250- Monitor blood pressure 2 to 3 hours after initial dose because of possible first-dose hypotension and ml bag) in 170 ml D5W or NSS to yield 4,000 mcg/ml. again after 24 hours to evaluate patient’s response Give I.V. drug using an infusion pump. If patient requires administration by feeding tube, place capsule in 60 ml of warm tap water. Stir until Monitor blood pressure continuously during therapy, preferably by continuous intra-arterial capsule shell dissolves and liquid contents are released into water (5 to 10 minutes). monitoring. Monitor heart rate and rhythm via ECG recordings continuously BETA 2 AGONIST ALPHA 2 ANTAGONIST Epinephrine, Ephedrine, Isoproterenol, Albuterol, Terbutaline, Metaproterenol Yohimbine (Obsolete) Benign prostatic hyperplasia, Hypertension associated with heart attacks and seizures due to inaccurate labeling and potential serious side effects. BETA ADRENERGIC ANTAGONISTS -olols AKA beta blockers which decrease heart rate, and a decrease in blood pressure usually follows. Bronchoconstriction also occurs. Reduces cardiac output and tachycardia, causes vasodilation, and decreases peripheral vascular resistance, which reduces blood pressure and cardiac workload. It blocks the release of the stress hormones adrenaline and noradrenaline in certain parts of the body. It decreases myocardial oxygen demand, which helps prevent anginal pain and death of myocardial tissue. Attaches to beta 2 receptors on bronchial cell membranes. It promotes the production of intracellular cyclic adenosine monophosphate (cAMP), which enhances the binding of intracellular calcium to the NURSING CONSIDERATION cell membrane. This action decreases the calcium concentration within cells and results in the relaxation Use cautiously in patients with bronchospastic lung disease because it may induce asthmatic attack, of smooth muscle and bronchodilation. and in patients with underlying skeletal muscle disease; isolated reports of myopathy and myotonia have occurred. NURSING CONSIDERATION Hypersensitivity to beta blockers. Administer pressurized inhalations of albuterol during second half of inspiration, when airways are Use cautiously in diabetic patients because it may mask tachycardia caused by hypoglycemia. open wider and aerosol distribution is moreeffective Monitor patient for heart failure. Monitor serum potassium level because albuterol may cause transient hypokalemia Stop the medication and notify prescriber if patient develops bradycardia, hypotension, or other Use cautiously in patients with cardiac disorders, diabetes mellitus, digitalis intoxication, serious adverse reaction. hypertension, hyperthyroidism, or history of seizures. Albuterol can worsen these conditions. 1.1 NONSELECTIVE BETA BLOCKERS block both beta1 and beta2 and should be used with extreme caution in any patient who has chronic obstructive pulmonary disease (COPD) or asthma. Ex: Carvedilol, Labetalol, Propranolol, Nadolol, Pindolol, Sotalol, Timolol MIXED (ALPHA AND BETA-AGONISTS) Epinephrine, NE, Ephedrine, Dopamine, Pseudoephedrine ADRENERGIC ANTAGONISTS DRUGS cAMP activates protein kinase A (PKA) which phosphorylates multiple proteins in smooth muscle cells leading to relaxation, or in airway epithelial cells to increased ciliary beating. Adrenergic antagonists, adrenergic blockers, sympatholytics They block the alpha- or beta-receptor sites by inhibiting the release of NE and epinephrine. 1.2 NONSELECTIVE BETA BLOCKERS Alpha 1 blocker Beta 1 blocker Beta 2 blocker: have greater affinity for certain receptors. If the desired effect is to decrease pulse rate and blood pressure, a selective beta1 blocker is given. BP decreases Ex: Atenolol, Metoprolol tartrate EYES miosis BLADDER reduces contraction PROSTATE reduces contraction decreases (reduces the HEART RATE force of contractions) BRONCHIOLES constricts UTERUS constricts inhibits glycogenolysis BLOOD GLUCOSE (decrease) ALPHA 1 ANTAGONISTS Phentolamine, Prazosin, Terazosin, Tamsulosin better suited for patients with asthma or restrictive airway disease. PARASYMPATHETIC NERVOUS SYSTEM -CHOLINERGIC SYSTEM-  PHARMACOLOGY NCM 106 PROF. DANLLED JAVIER | S.Y 2024-2025 | DOMINGO,ANGELYN Cardiovascular __ HR, __ BP 2 RECEPTORS __ tone and motility of smooth muscle of stomach and intestine, __ Gastrointestinal peristalsis, and relaxed sphincter muscles NICOTINIC RECEPTORS Contraction of muscles of the urinary bladder, increased tone of ureters, Genitourinary stimulated by nicotine alkaloid relaxed bladder sphincter muscles, and stimulated urination function within the CNS and at the neuromuscular junction (connection between the terminal end of a Increased pupil constriction or miosis and increased accommodation motor nerve and a muscle) Ocular (flattening or thickening of eye lens for distant or near vision) mediate fast excitatory neurotransmission at the neuromuscular junction and at autonomic ganglia Glandular __ salivation, perspiration, and tears MUSCARINIC RECEPTORS Bronchial Stimulation of bronchial smooth muscle contraction and increased bronchial secretions stimulated by muscarine alkaloid Increased neuromuscular transmission and maintenance of muscle strength function in both the PNS and CNS, mediating innervation to visceral organs (sweat, lacrimal, salivary Striated muscle and tone mammary, and digestive glands) respond more slowly than nicotinic receptors CHOLINERGIC ANTAGONISTS Also known as parasympatholytics or anticholinergics Drugs that inhibit the actions of acetylcholine by occupying the acetylcholine receptors Major responses to anticholinergics: decrease in GI motility decrease in salivation mydriasis increase in pulse rate CHOLINERGIC AGONISTS Also known as parasympathomimetics Drugs that stimulate the parasympathetic nervous system 2 types of cholinergic agonists: 1. Direct-Acting Cholinergic Agonists Anticholinergic Response: The anticholinergic drug occupies the receptor sites, blocking acetylcholine. 2. Indirect-Acting Cholinergic Agonists ACh, Acetylcholine;, D, anticholinergic drug. 1.1 DIRECT-ACTING CHOLINERGIC AGONISTS Other effects of anticholinergics: which act on receptors to activate a tissue response decreased bladder contraction urinary retention decreased rigidity and tremors related to neuromuscular excitement act as an antidote to the toxicity caused by cholinesterase inhibitors and organophosphate ingestion EFFECTS OF CHOLINERGIC ANTAGONISTS: Cardiovascular increase HR with large doses, small doses can decrease HR Relaxed smooth muscle tone of GI tracts decreased GI motility and Gastrointestinal peristalsis; gastric and intestinal secretions are decreased Relaxed bladder detrusor muscle and increased constriction of internal Genitourinary Cholinergic Agonists resemble aceetylcholine and act directly on the receptor sphincter = urinary retention Acetylcholine Ocular Dilated pupils (mydriasis) and paralyzed ciliary muscles (cycloplegia) Directing-acting muscarinic Glandular Salivation, perspiration, and bronchial secretions are decreased Bethanechol (postoperative urinary retention, postpartum urinary retention), Carbachol (IOP) Pilocarpine, Cevimeline (Sjogren's syndrome)e) Bronchial Bronchodilation Direct-acting nicotinic Tremors and rigidity of muscles are decreased; drowsiness, disorientation, Striated muscle and hallucinations can result from large doses. Nicotine, Varenicline, Lobeline Succinylcholine, Suxamethonium chloride MUSCARINIC ANTAGONISTS: 1.2 INDIRECT-ACTING CHOLINERGIC AGONISTS- Atropine, Homatropine, Cyclopentolate, Tropicamide which inhibit the action of the enzyme cholinesterase (ChE), also called acetylcholinesterase (AChE) blocks ALL muscarinic receptors Ipratropium bromide, Tiotropium Scopolamine/Hyoscine Dicyclomine Oxybutynin, Darifenacin, Fesoterodine (Overactive bladder) Pirenzepine, Telenzepine (PUD) NICOTINIC ANTAGONISTS: Hexamethonium, Trimethaphan, Mecamylamine Obsolete use in hypertension Tubocurarine, Pancuronium, Atracurium, Vecuronium Skeletal muscle relaxation prior to surgery Indirect-acting parasympathomimetic (cholinesterase inhibitor). Cholinesterase inhibitors inactivate the enzyme acetylcholinesterase (cholinesterase), thus permitting acetylcholine to react to the receptor. ACh, Acetylcholine; AChE, acetylcholinesterase or cholinesterase; D, cholinergic agonist; DD, cholinesterase inhibitor (anticholinesterase). Edrophonium (Myasthenia gravis) Carbamates (-stigmines) Organophosphates (Parathion, Malathion, Tabun, Sarin, Soman) Drugs for Alzheimer’s disease Edrophonium (Myasthenia gravis) Carbamates (-stigmines) Organophosphates (Parathion, Malathion, Tabun, Sarin, Soman) Drugs for Alzheimer’s disease EFFECTS OF CHOLINERGIC AGONISTS: